A Phase III Randomised Clinical Trial of Ultrasound Groin Monitoring Versus Groin Lymph Node Dissection to De-Escalate the Extent of Surgery in Vulvar Cancer
This study is a phase II, open label, multicentre, three-group, randomised clinical trial. The primary aim of this study is to determine whether intensive groin ultrasound monitoring (1) is effective and safe to replace invasive groin lymph node dissection (LND) to manage vulvar cancer, (2) decreases the morbidity associated with vulvar cancer surgery, and (3) is cost effective.
Study details:
Treatment of vulvar cancer causes significant morbidity. Despite being a rare cancer, at least 2500 survivors of vulvar cancer live in Australia. Most survivors live with the detrimental, life-long impacts resulting from their cancer treatment because there are currently no alternatives to mitigate these impacts.
The personal and societal burden this entails is significant. To control such cancer-associated burden is a national priority. Clinical palpation of the groin region and computed tomography (CT) scans do not reliably detect groin node involvement.
Hence, current clinical guidelines recommend all women diagnosed at apparent Stage I or II have a surgical groin LND. This can be performed as a full IFL (full LND) to remove all groin nodes, or as a sentinel node biopsy (SNB) to remove selected (one or two) nodes. SNB is less invasive, however, is appropriate only for vulvar cancers \<4cm in diameter and unifocal tumours (\~50% of all Stage I and II vulvar cancers).
SNB is also associated with a false negative rate (10%) that increases the risk of undetected nodes. In 25% of cases (\~80 Australian women per year), groin LND will reveal positive nodes (i. e.
, metastases), which triggers a referral for radiation treatment. If positive groin nodes are missed, and over time become enlarged, clinically palpable and attached to the overlying skin, \>90% of women will die within 12 months, despite subsequent treatment. Conversely, if groin node involvement is detected early (e.
g. , by ultrasound) while still small, survival outcomes are excellent. Ultrasound technology is potentially as accurate as LND due to recent advances in resolution and technologies such as 2D/3D volumetric assessments and tissue flow.
Furthermore, ultrasound is superior to medical resonance imaging (MRI), and to standard CT and positron emission tomography (PET) scans in capturing groin node involvement because it has a higher resolution, avoids harmful radiation and the technology is readily accessible outside of high-volume metropolitan areas. The investigators propose to reduce surgical morbidity by replacing upfront groin LND for vulvar cancer patients with serial high-resolution ultrasound to detect groin metastases. Groin LND will only be necessary for the few women with ultrasound-detected metastases when they are still small.
The ANVU trial will determine the value of serial groin ultrasound examinations in stage 1 and 2 vulvar cancer patients and whether it is feasible and safe to de-escalate the extent of vulvar cancer surgery to achieve improved outcomes for affected patients. Australian women with this rare cancer bear an unacceptably high (and potentially avoidable) treatment-related burden. This clinical trial is the first step to address this problem in a novel yet pragmatic way.
The overall outcome of ANVU is a novel, less invasive alternative to vulvar cancer LND associated with significantly less morbidity, without compromising survival.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
- Females, over 18 years, with histologically confirmed SCC, adenocarcinoma, or melanoma of the vulvar
- Clinically stage 1 or 2 on medical imaging (CT or MRI scan of pelvis, abdomen, and chest), without evidence of regional or distant metastatic disease
- Undergo IFL/SNB according to local clinical practice management guidelines
- Willing and able to comply with all study requirements, timing and/or nature of required assessments.
- Signed written informed consent
- Negative (serum or urine) pregnancy (BHCG) test ≤ 30 days of surgery ONLY in pre-menopausal women and women < 2 years after the onset of menopause.
Exclusion criteria
- Women with non-invasive vulvar conditions (e.g. non-invasive non-mammary Paget's disease)
- SCC of the vulvar with depth of invasion ≤1 mm
- Clinical or medical imaging evidence of regional and/or distant metastatic disease
- Serious concomitant systemic disorders incompatible with the study (at the discretion of the investigator)
- Other prior malignancies <5 years before inclusion, except for successfully treated keratinocyte skin cancers, or ductal carcinoma in situ
- Estimated life expectancy of ≤6 months
Eligibility
Age eligible for study : NA
Healthy volunteers accepted : No
Gender eligible for study: FEMALE
Things to know
Study dates
Study start:
Primary completion:
Study completion finish:
Study type
OTHER
Phase
- PHASE3
Study ID
NCT06476639
Intervention or treatment
DIAGNOSTIC_TEST: High-resolution bilateral groin ultrasound monitoring
Conditions
- Vulvar Cancer Stage I
- Vulvar Cancer Stage II
- Lymph Node Metastasis
- Groin Node
- Ultrasound Therapy; Complications
You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.
Research sites nearby
Closest Location:
John Hunter Hospital
Select from list below to view details:
John Hunter Hospital
Newcastle, New South Wales, Australia
The Royal North Shore Hospital
Sydney, New South Wales, Australia
The Royal Darwin Hospital
Darwin, Northern Territory, Australia
The Wesley Hospital
Auchenflower, Queensland, Australia
Loading map...
Who is running the clinical trial?
Queensland Centre for Gynaecological Cancer
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
EXPERIMENTAL: Participants with normal/negative baseline groin ultrasounds - Intervention Group
| Diagnostic Test: High-resolution bilateral groin ultrasound monitoring |
NO_INTERVENTION: Participants with normal/negative baseline groin ultrasounds - Standard Group
| |
NO_INTERVENTION: Participants with suspicious/indeterminate baseline groin ultrasound - Standard Treatment
|
What is the study measuring?
Primary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of enlarged clinically palpable groin nodes (groin metastases) in women with vulvar cancer randomised to serial high-resolution groin ultrasound monitoring compared to standard upfront surgical groin LND. | Determine the incidence of palpable, fixed to skin and histologically positive groin nodes in women with vulvar cancer randomised to serial high-resolution groin ultrasound monitoring compared to standard upfront surgical groin LND. | 12 months after surgery |
Secondary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Patient Reported Outcomes (PROMs) | Compare PROMS between the groups, as measured by the EuroQoL-5D and FACT-V questionnaires, at baseline, 8 weeks, 6 months, and 12 months. | 12 months after surgery |
| Health Related Quality of Life (HRQL) | Compare HRQL between the groups, as measured by the EuroQoL-5D and FACT-V questionnaires at baseline, 8 weeks, 6 months and 12 months. | 12 months after surgery |
| Pain | Compare pain levels between the groups | 12 months after surgery |
| Adverse events | Compare adverse events between the groups | 12 months after surgery |
| Lower limb lymphoedema | Compare the incidence of lower limb lymphoedema between the groups | 12 months after surgery |
| Cost-effectiveness | Compare cost effectiveness between the groups | 12 months after surgery |
| Disease-free survival | Compare disease-free survival between the groups | 12 months after surgery |
| Overall survival | Compare overall survival between the groups | 12 months after surgery |
| Clinical accuracy of high-resolution serial ultrasound to predict groin lymph node involvement | Determine the diagnostic accuracy of pre-operative, standardised, high-resolution groin ultrasound to identify groin node metastasis | 12 months after surgery |
| Utility of circulating tumour DNA to reliably reflect the presence or absence of positive groin lymph nodes | Assess the role of circulating tumour DNA to accurately determine the burden of disease (positive lymph nodes) in vulvar cancer, assist with risk stratification and aid disease surveillance | Study duration of up to 15 years |
| Utility of plasma to reliably reflect the presence or absence of positive groin lymph nodes | Assess the role of plasma to accurately determine the burden of disease (positive lymph nodes) in vulvar cancer, assist with risk stratification and aid disease surveillance | Study duration of up to 15 years |
| Utility of serum to reliably reflect the presence or absence of positive groin lymph nodes | Assess the role of serum to accurately determine the burden of disease (positive lymph nodes) in vulvar cancer, assist with risk stratification and aid disease surveillance | Study duration of up to 15 years |
| Utility of tumour mutations to reliably reflect the presence or absence of positive groin lymph nodes | Assess the role of tumour mutations to accurately determine the burden of disease (positive lymph nodes) in vulvar cancer, assist with risk stratification and aid disease surveillance | Study duration of up to 15 years |
References
Clinical Trials Gov: A Phase III Randomised Clinical Trial of Ultrasound Groin Monitoring Versus Groin Lymph Node Dissection to De-Escalate the Extent of Surgery in Vulvar CancerOther trials to consider
Loading suggested trials...
